Stillbirth and neonatal death in relation to radiation exposure before conception: a retrospective cohort study.
Stillbirth and neonatal death in relation to radiation exposure before conception: a retrospective cohort study.
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DOI：
10.1016/s0140-6736(10)60752-0
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发表时间：
2010-08-21
期刊：
影响因子：
168.9
通讯作者：
Boice, John D., Jr.
中科院分区：
文献类型：
--
作者：
Signore, Lisa B.;Mulvihill, John J.;Green, Daniel M.;Munro, Heather M.;Stovall, Marilyn;Weathers, Rita E.;Mertens, Ann C.;Whitton, John A.;Robison, Leslie L.;Boice, John D., Jr.
对癌症儿童进行诱变治疗的生殖影响尚不清楚。通过研究不良妊娠结局的风险，我们间接评估了接受放疗和化疗的儿童癌症幸存者的后代生殖细胞损伤的传播风险。我们在儿童癌症幸存者研究（CCSS）中进行了一项回顾性队列分析，分析了儿童癌症幸存者的后代中死产和新生儿死亡的风险。CCSS中的患者在首次诊断符合条件的癌症时年龄小于21岁，在25家美国机构和1家加拿大机构接受治疗，并在诊断后存活至少5年。我们量化了给予患者的化疗，以及对睾丸、卵巢、子宫和垂体的孕前辐射剂量，并使用泊松回归分析将这些与死产或新生儿死亡的风险相关。在1148名男性和1657名女性儿童癌症幸存者中，有4946人怀孕。睾丸辐射（16/1270 [1%];校正相对风险0.8 [95% CI 0.4 - 1.6];平均剂量0.53戈伊[SD 1.40]）和垂体510例中17例（3%），> 20·00戈伊者1·1例（0·5-2·4）;女性平均剂量10·20戈伊[13·0]），以及使用烷化剂的化疗（1195名女性中有26名[2%]，0.9 [0.5 - 1.5]; 732名男性中有10名[1%]，1.2 [0.5 - 2.5]）与死产或新生儿死亡风险增加无关。子宫和卵巢照射剂量大于10·00戈伊时，死产和新生儿死亡风险显著增加（5/28，18%，9·1 [3·4-24·6]）。在月经初潮前接受治疗的女孩中，子宫和卵巢的低剂量照射（1·00-2·49戈伊）显著增加了死产或新生儿死亡的风险（69例中有3例[4%]，4·7例[1·2-19·0]）。我们的研究结果并不支持可遗传的遗传变化影响男性生殖腺照射后后代死胎和新生儿死亡风险的观点。然而，子宫和卵巢照射对后代有严重的不良影响，可能与子宫损伤有关。在青春期前接受大剂量盆腔照射的妇女妊娠时，应谨慎处理。
The reproductive implications of mutagenic treatments given to children with cancer are not clear. By studying the risk of untoward pregnancy outcomes, we indirectly assessed the risk of transmission of germline damage to the offspring of survivors of childhood cancer who were given radiotherapy and chemotherapy. We did a retrospective cohort analysis, within the Childhood Cancer Survivor Study (CCSS), of the risk of stillbirth and neonatal death among the offspring of men and women who had survived childhood cancer. Patients in CCSS were younger than 21 years at initial diagnosis of an eligible cancer, were treated at 25 US institutions and one Canadian institution, and had survived for at least 5 years after diagnosis. We quantified the chemotherapy given to patients, and the preconception radiation doses to the testes, ovaries, uterus, and pituitary gland, and related these to the risk of stillbirth or neonatal death using Poisson regression analysis. Among 1148 men and 1657 women who had survived childhood cancer, there were 4946 pregnancies. Irradiation of the testes (16 [1%] of 1270; adjusted relative risk 0·8 [95% CI 0·4–1·6]; mean dose 0·53 Gy [SD 1·40]) and pituitary gland (17 [3%] of 510, 1·1 [0·5–2·4] for more than 20·00 Gy; mean dose 10·20 Gy [13·0] for women), and chemotherapy with alkylating drugs (26 [2%] of 1195 women, 0·9 [0·5–1·5]; ten [1%] of 732 men, 1·2 [0·5–2·5]) were not associated with an increased risk of stillbirth or neonatal death. Uterine and ovarian irradiation significantly increased risk of stillbirth and neonatal death at doses greater than 10·00 Gy (five [18%] of 28, 9·1 [3·4–24·6]). For girls treated before menarche, irradiation of the uterus and ovaries at doses as low as 1·00–2·49 Gy significantly increased the risk of stillbirth or neonatal death (three [4%] of 69, 4·7 [1·2–19·0]). Our findings do not support concern about heritable genetic changes affecting the risk of stillbirth and neonatal death in the offspring of men exposed to gonadal irradiation. However, uterine and ovarian irradiation had serious adverse effects on the offspring that were probably related to uterine damage. Careful management is warranted of pregnancies in women given high doses of pelvic irradiation before puberty.